One of the common problems of poorly water-soluble drugs is that they provide low bioavailability and/or higher variability in bioavailability as a result of poor water solubility and slow dissolution. Formation of a soluble salt form for an insoluble compound is often a means to increase drug solubility in an aqueous medium, and hence improve dissolution rate and ultimately enhance bioavailability. In some cases, even a soluble salt of a drug has high bio-variability and/or poor bioavailability. For example, upon exposure to aqueous medium, the salt may undergo a dissolution process during which the solid particle dissolves and then diffuses. However, during the dissolution process, the salt can be dissociated to a non-ionized form. The non-ionized form may achieve supersaturation and then precipitate out either on the exterior surface of the salt particle or in the bulk medium. This prevents further dissolution of the salt, and results in low bioavailability with high variability.
It is also desirable to deliver a pharmaceutical composition to a patient as a tablet or capsule, which may provide greater chemical stability and improved patient convenience compared to semi-solid or solution dosage forms.
There is, therefore, a need for improved formulations of water-insoluble drugs and, in particular, improved formulations of phenyl uracil compounds such as (E)-N-(4-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxystyryl)phenyl)methanesulfonamide and its salts.